Angiogenesis is the physiological process by which new blood vessels form from preexisting blood vessels. The concept of inhibiting angiogenesis as a therapeutic strategy, particularly for treating tumors and cancers, has been discussed for several decades, and is now widely considered to be a promising approach for the treatment of a range of pathologies and disease states in which vascular proliferation is a component. Anti-angiogenesis strategies have now been pursued not only as anti-cancer therapies, but also for the treatment of arthritis, retinopathies, heart disease, and circulatory problems. Accordingly, experimental animal models of angiogenesis are important for studying angiogenesis and the growth of blood vessels, evaluating the effects of different compounds on angiogenesis, and for screening compounds to identify compounds having anti-angiogenic or pro-angiogenic activity.
The cornea has been considered an ideal model of in vivo angiogenesis because it is avascular, and therefore any vascular development (i.e., development of new blood vessels) can usually be directly attributed to a substance or compound applied to the corneal area of the eye. Therefore, many animal models developed to study in vivo angiogenesis are models of corneal angiogenesis. These animal models are commonly produced by introducing a cornea pocket, or iris implant, into the eye of an animal.
In the cornea pocket model, an inducer of angiogenesis, such as tumor tissue, a cell suspension, or growth factor is placed into a pocket formed in the cornea, which induces the formation of new blood vessels. However, formation of the cornea pocket is often a difficult procedure, typically performed by lamellar dissection with a scalpel to create a space or “pocket” in the cornea, into which the inducer of angiogenesis is introduced. Due to the surgical nature of the procedure, complications often result from the procedure including problems related to the anesthetic agent used, perforation of the anterior chamber of the eye during dissection, inadequate preparation of the inducer of angiogenesis, and angiogenesis resulting from the surgical wound itself or sutures used to stitch the surgical wound. Moreover, inflammatory reactions can occur due to tissue manipulation and suturing, as well as in response to the inducer of angiogenesis inserted into the cornea pocket, which is often a foreign substance. Reactions to the insertion of foreign materials in the eye can also cause fibrosis, which is the formation of excess fibrous connective tissue in an organ or tissue. Fibrosis is usually the result of a reparative or reactive process.
Moreover, to the best of the inventor's knowledge, there are currently no animal models of corneal ectatic diseases, such as corneal keratoconus. Corneal ectasia is the progressive bulging of the cornea due to thinning or weakening of the cornea, accompanied by vision deterioration, vision impairment, or both. Corneal keratoconus is one of the more common corneal ectatic diseases, and is characterized by a structural distortion of the cornea from the typical rounded shape to a conical shape that protrudes, or bulges, outward from the corneal area of the eye. Animal models of corneal ectatic diseases would provide tools for studying these diseases in vivo.